Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood – R&D @Worcester Polytechnic Institute, Micro and Nanotechnology Lab
Static micro-array isolation, dynamic time series classification, capture and enumeration of spiked breast cancer cells in blood: the nanotube–CTC chip
Farhad Khosravi1, Patrick J Trainor2, Christopher Lambert3, Goetz Kloecker4, Eric Wickstrom5, Shesh N Rai2,6 and Balaji Panchapakesan1
Published 29 September 2016 • © 2016 IOP Publishing Ltd
Nanotechnology (2016). DOI: 10.1088/0957-4484/27/44/44LT03
Researchers build liquid biopsy chip that detects metastatic cancer cells in blood: One blood sample can be tested for a comprehensive array of cancer cell markers.
“Imagine going to the doctor for your yearly physical,” he said. “You have blood drawn and that one blood sample can be tested for a comprehensive array of cancer cell markers. Cancers would be caught at their earliest stage and other stages of development, and doctors would have the necessary protein or genetic information from these captured cells to customize your treatment based on the specific markers for your cancer. This would really be a way to put your health in your own hands.”
[T]he WPI device is also highly effective in separating cancer cells from the other cells and material in the blood through differential settling.
“White blood cells, in particular, are a problem, because they are quite numerous in blood and they can be mistaken for cancer cells,” he said. “Our device uses what is called a passive leukocyte depletion strategy. Because of density differences, the cancer cells tend to settle to the bottom of the wells (and this only happens in a narrow window), where they encounter the antibodies. The remainder of the blood contents stays at the top of the wells and can simply be washed away.”
In addition to capturing tumor cells, Panchapakesan says the chip will also latch on to tiny structures called exosomes, which are produced by cancers cells and carry the same markers. “These highly elusive 3-nanometer structures are too small to be captured with other types of liquid biopsy devices, such as microfluidics, due to shear forces that can potentially destroy them,” he noted. “Our chip is currently the only device that can potentially capture circulating tumor cells and exosomes directly on the chip, which should increase its ability to detect metastasis. This can be important because emerging evidence suggests that tiny proteins excreted with exosomes can drive reactions that may become major barriers to effective cancer drug delivery and treatment.”
The device developed by Panchapakesan’s team includes an array of tiny elements, each about a tenth of an inch (3 millimeters) across. Each element has a well, at the bottom of which are antibodies attached to carbon nanotubes. Each well holds a specific antibody that will bind selectively to one type of cancer cell type, based on genetic markers on its surface. By seeding elements with an assortment of antibodies, the device could be set up to capture several different cancer cells types using a single blood sample. In the lab, the researchers were able to fill a total of 170 wells using just under 0.3 fluid ounces (0.85 milliliter) of blood. Even with that small sample, they captured between one and a thousand cells per device, with a capture efficiency of between 62 and 100 percent.
The carbon nanotubes used in the device act as semiconductors. When a cancer cell binds to one of the attached antibodies, it creates an electrical signature that can be detected. These signals can be used to identify which of the elements in the array have captured cancer cells. Those individual arrays can then be removed and taken to a lab, where the captured cells can be stained and identified under a microscope. In the lab, the binding and electrical signature generation process took just a few minutes, suggesting the possibility of getting same-day results from a blood test using the chip, Panchapakesan says.
Balaji Panchapakesan – List of Recent Publications